A Study of LY3381916 Alone or in Combination With LY3300054 in Participants With Solid Tumors

A Phase 1a/1b Study of an Anti-IDO-1 Agent (LY3381916) Administered Alone or in Combination With Anti- PD-L1 Checkpoint Antibody (LY3300054) in Solid Tumors

The purpose of this study is to evaluate the safety of the study drug LY3381916 administered alone or in combination with anti-programmed cell death ligand 1 (PD-L1) checkpoint antibody (LY3300054).

Study Overview

• Status: Terminated
• Conditions: Renal Cell Carcinoma; Solid Tumor; Non Small Cell Lung Cancer; Triple Negative Breast Cancer
• Intervention / Treatment: Drug: LY3381916; Drug: LY3300054

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1000
    • Institut Jules Bordet
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
• Denmark
  • Copenhagen, Denmark, 2100
    • Finsen Institute
• France
  • Villejuif Cedex, France, 94805
    • Gustave Roussy
• Italy
  • Ancona, Italy, 60100
    • Azienda Ospedaliera Umberto I
  • Milano
    • Monza, Milano, Italy, 20052
      • Azienda Ospedaliera San Gerardo
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Hospital Clínico Universitario Virgen de la Victoria
• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Iu Simon Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute SCRI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Dose escalation phase: Participant must have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic.
• Dose expansion B1: Metastatic TNBC participants who have not received prior PD-1/L1 treatment.
• Dose expansion B2: Metastatic NSCLC participants who have progressed on prior PD-L1/L1 treatment.
• Dose expansion B3: Metastatic clear cell carcinoma RCC who have progressed on prior PD-L1/L1 treatment.
• Have adequate organ function.
• Have a performance status (PS) of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Are able and willing to provide required, newly acquired tumor biopsies.
• Have discontinued previous treatments for cancer.
• Are able to swallow capsules.

Exclusion Criteria:

• Currently enrolled in a clinical study.
• Have known symptomatic central nervous system metastases or carcinomatous meningitis.
• Have a serious concomitant systemic disorder.
• Have a symptomatic human immunodeficiency virus infection or symptomatic activated/reactivated hepatitis B or C.
• Have a significant cardiac condition.
• Have previously received an indoleamine- 2,3-dioxygenase (IDO) inhibitor.
• Have an active autoimmune disease or currently require immunosuppression of >10 milligrams of prednisone or equivalent per day.
• Have interstitial lung disease or (noninfectious) pneumonitis, participants with a history of (noninfectious) pneumonitis that required steroids to assist with management.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3381916 Escalation; LY3381916 administered orally.	Drug: LY3381916; IDO-1 inhibitor administered orally
Experimental: LY3381916 + LY3300054 Escalation; LY3381916 administered orally and LY3300054 administered intravenously (IV).	Drug: LY3381916; IDO-1 inhibitor administered orally; Drug: LY3300054; PD-L1 inhibitor administered IV
Experimental: LY3381916 Expansion; LY3381916 administered orally.	Drug: LY3381916; IDO-1 inhibitor administered orally
Experimental: LY3381916 + LY3300054 Expansion B1; Metastatic triple negative breast cancer (TNBC) LY3381916 administered orally and LY3300054 administered IV.	Drug: LY3381916; IDO-1 inhibitor administered orally; Drug: LY3300054; PD-L1 inhibitor administered IV
Experimental: LY3381916 + LY3300054 Expansion B2; Metastatic non-small cell lung cancer (NSCLC) LY3381916 administered orally and LY3300054 administered IV.	Drug: LY3381916; IDO-1 inhibitor administered orally; Drug: LY3300054; PD-L1 inhibitor administered IV
Experimental: LY3381916 + LY3300054 Expansion B3; Metastatic clear cell carcinoma renal cell carcinoma (RCC) LY3381916 administered orally and LY3300054 administered IV.	Drug: LY3381916; IDO-1 inhibitor administered orally; Drug: LY3300054; PD-L1 inhibitor administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Dose Limiting Toxicities (DLTs)	Number of participants with DLTs	Baseline through Cycle 1 (28 Day Cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR)	ORR: Percentage of participants with a CR or PR	Baseline through Measured Progressive Disease (Estimated up to 12 Months)
Duration of Response (DOR)	DOR	Date of CR or PR to Date of Objective Progression or Death Due to Any Cause (Estimated up to 12 Months)
Time to Response (TTR)	TTR	Baseline to Date of CR or PR (Estimated up to 12 Months)
Disease Control Rate (DCR): Percentage of Participants who Exhibit Stable Disease (SD), CR or PR	DCR: Percentage of participants who exhibit SD, CR or PR	Baseline through Measured Progressive Disease (Estimated up to 12 Months)
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY3381916	PK: Cmax of LY3381916	Predose Lead in Day 1 through Cycle 3 Day 1
PK: Area Under the Plasma Concentration Curve (AUC) of LY3381916	PK: AUC of LY3381916	Predose Lead in Day 1 through Cycle 3 Day 1
PK: Cmax of LY3381916 Administered in Combination with LY3300054	PK: Cmax of LY3381916 administered in combination with LY3300054	Predose Cycle 1 Day 1 through Cycle 3 Day 1
PK: AUC of LY3381916 Administered in Combination with LY3300054	PK: AUC of LY3381916 administered in combination with LY3300054	Predose Cycle 1 Day 1 through Cycle 3 Day 1
PK: Cmax of LY3300054 Administered in Combination with LY3381916	PK: Cmax of LY3300054 administered in combination with LY3381916	Predose Cycle 1 Day 1 through Cycle 3 Day 1
PK: Minimum Plasma Concentration (Cmin) of LY3300054 Administered in Combination with LY3381916	PK: Cmin of LY3300054 administered in combination with LY3381916	Predose Cycle 1 Day 1 through Cycle 3 Day 1
Progression Free Survival (PFS)	PFS	Baseline to Objective Progression or Death Due to Any Cause (Estimated Up to 12 Months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of LY3381916 Alone or in Combination With LY3300054 in Participants With Solid Tumors

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2017
• Primary Completion (Actual): February 7, 2020
• Study Completion (Actual): May 4, 2020

Study Registration Dates

• First Submitted: November 9, 2017
• First Submitted That Met QC Criteria: November 10, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): June 9, 2020
• Last Update Submitted That Met QC Criteria: June 8, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: IDO Inhibitor; IDO-1 Inhibitor; IDO1 Inhibitor
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Kidney Neoplasms; Breast Neoplasms; Carcinoma, Renal Cell; Triple Negative Breast Neoplasms
• Other Study ID Numbers: 16786; I9L-MC-JZCA (Other Identifier: Eli Lilly and Company); 2017-002693-39 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No